PB1906: IS THERE A PLACE FOR IMATINIB IN THE FIRST-LINE TREATMENT OF CHRONIC MYELOID LEUKEMIA CHRONIC PHASE: REAL LIFE DATA FROM UNIVERSITY CENTER AFTER LONG PERIOD OF FOLLOW-UP
Authors: D. Lekovic, J. Jovanovic, V. Djordjevic, V. Milosevic, J. Bodrozic, A. Bogdanovic
Journal: HemaSphere (2022)

Background: The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) significantly changed the natural course of the disease and increased the overall survival of these patients. Any of three TKIs (imatinib, nilotinib, dasatinib) can be used in the first treatment line (I TL). So far, no significant survival difference between imatinib and second generation TKIs has been observed. The place of imatinib in first-line therapy of CML is not yet clearly defined. Aims: of our study was to analyze the cytogenetic and molecular response of patients treated with imatinib 400mg daily in the I TL as well as to identify their corelation with duration of survival. Methods: This retrospective study included 331 consecutive CML patients (chronic phase) who were diagnosed and treated at Clinic of Hematology, University Clinical Center of Serbia in period of 20 years. Diagnosis of CML was made according to the ELN criteria. Data were extracted from medical records. In all patients Sokal, Hasford, EUTOS and ELTS prognostic scores were analyzed. Results: The median age of patients at diagnosis was 52 years (range 18-82), with 28.4% ≥ 60 years and 51.2% were male. Hepatomegaly had 25.7% of patients while splenomegaly 71.6%. The cytogenetic response during imatinib treatment was as follows: 72.8% achieved CCyR, 9.1% majorCyR, 3.3% minorCyR while 14.2% had no response. After median follow-up of 88 months, 40.5% was switched to another therapy due to primary resistance (26.6%), secondary resistance mainly incompetence in taking the drug (11.5%) and adverse events (2.4%; 2/6 patients had hepatic toxicity verified by liver biopsy in the first 6 months of imatinib treatment). Patients with primary resistance had significantly higher white blood cell counts (p=0.019), percentage of blasts in peripheral blood (p=0.019), and spleen size (p=0.004) at the time of diagnosis than the patients with secondary resistance. Significant predictors of survival were: achievment of CCyR (p=0.001), percentage of blasts in peripheral blood (p=0.008) and Hasford score (p=0.010). The median survival of patients who achieved CCyR during treatment with imatinib at a dose of 400 mg daily was 218 months (95% CI, 204-232) while in those who did not achieve was 152 months (95% CI, 120-185) (p = 0.001). Patients with CCyR on imatinib therapy achieved MR3.0 in 45,6%, MR4.0 in 27.4%, MR4.5 in 14.5% and MR5.0 in 12.5% of the patients. Overall survival after 5, 10, and 15-years was 95.7%, 92,5%, and 84,2% respectively. Fatal outcome had 17.8% of patients with the cause being the progression of underlying disease in 51% and comorbidities in 49% mostly cerebrovascular stroke (7 pts), heart disease (7 pts) and secondary malignancies (6 pts).nalyzed. Summary/Conclusion: During the treatment with imatinib 400mg in I TL, 2/3 of patients achieved and maintained CCyR. Patients with achieved CCyR had significantly longer survival and 54% of patients achieved at least deep molecular response (MR4.0). Survival after 10 years is over 90% without fatal adverse events. Due to imatinib resistance during follow-up, 40.5% of patients require the use of newer generation of TKI. TKI selection should be based on treatment goals, age and comorbidities and should take into consideration the adverse event profile of the available drugs.